Embodiments of the present invention relate to the detection of biochemical substances using a giant magnetoresistive effect.
The detection of minute quantities of biochemical substances in a specimen of animal body fluid is important, for example, in the early detection of disease. Conventional methods of specimen analysis that are feasible in a commercial setting include Enzyme Linked Immunosolvent Assay (ELISA), Western blot, Immunofluorescent, and Heme Agglutination (HA). These methods may be performed automatically by equipment including the xe2x80x9cSystem 36 AutoBlotxe2x80x9d marketed by Genelabs Diagnostics (Singapore) a subsidiary of Genelabs Technologies, Inc.; or the xe2x80x9cAutomated RIBA Processorxe2x80x9d marketed by Chiron Corp. Other laboratory instrumentation may be used manually, including an ELISA plate reader, a fluorometer, and/or a luminometer. Conventional automatic equipment is bulky and expensive to acquire and maintain. And, manual equipment is labor intensive to use. Consequently, specimen analysis is costly. In some communities, a lack of specimen analysis has led to lengthy turn around delays. Such costs and delays interfere with the wide application of specimen analysis as a diagnostic practice. As a result, disease in animals including humans continues unchecked in its early stages.
A conventional biochemical assay performed in a laboratory may include the detection of microscopic paramagnetic particles (PMPs) bound to a giant magnetoresistive (GMR) sensor by specific intermolecular recognition bonds. PMPs are detected as a difference in the resistance of a GMR sensor having a bound PMP compared to a reference GMR sensor having no bound PMP. The difference may be detected using sinusoidal magnetic bias for the GMR sensors and a conventional lock-in amplifier technique. Accuracy of the assay depends in part on the removal of PMPs not bound according to the specific intermolecular recognition bond of interest.
The biochemical assay described above is prohibitively expensive for commercial application outside a laboratory setting. Part of this cost is in labor intensive steps including manual preparation of the specimen in combination with PMPs and manual removal of PMPs to improve assay accuracy. Another part of the cost becomes prohibitive as the number specimens to be tested in a given period of time is increased to a commercially practical level. Without method steps that prevent exposure of common surfaces to more than one specimen, an unsatisfactory risk of false positive assays may result.
In light of the demand for high volume biochemical assay services in combination with the lack of satisfactory techniques for maintaining low cost per specimen and low probability of false positive results, the need remains for improved systems and methods for biochemical assay.
A system for making a biochemical assay of each of a plurality of provided specimens, according to various aspects of the present invention, includes a plurality of receptacles, a sensor for providing a resistance, a mechanism, and a controller. Each receptacle contains a specimen and includes a surface for binding a paramagnetic particle (PMP) to the surface. When biased by a magnetic field, the presence of a PMP affects the resistance of the sensor in accordance with a giant magnetoresistive effect. The mechanism positions each respective surface in working proximity to the sensor for providing a respective resistance. The controller controls the mechanism for recording indicia of each respective resistance.
By providing a receptacle for each specimen, apart from the sensor, each receptacle may be discarded and the sensor reused without risk of contact of the sensor with more than one specimen. Such isolation avoids contamination between specimens and consequently avoids false positive assay results.
Because no specimen comes in contact with the sensor, the device may quickly perform an assay on each of a large number of specimens. The cost and time involved in repeated sterilization of the sensor is avoided.
In a variation, a system for making a biochemical assay of a provided plurality of specimens, according to various aspects of the present invention, includes a receptacle for each specimen, a sensor for providing a resistance, and a detector. Each receptacle includes a surface for binding a paramagnetic particle to the surface. The sensor provides a resistance according to a giant magnetoresistive effect when the sensor is positioned in working proximity to each respective surface. And, the detector, being coupled to the sensor, provides a signal that conveys indicia of each respective resistance.
In a variation, a plurality of sensors is arranged in an array coupled to a differential amplifier. The array is addressed by a row ring counter and a column ring counter. Each addressed cell is coupled in turn in a bridge circuit to the differential amplifier. The differential amplifier provides a signal that conveys indicia of the resistance of each sensor according to a sequence.
By forming the array, ring counters, and differential amplifier as an integrated circuit, coupling the plurality of sensors to the detector is simplified. In operation, an assay of a specimen in working proximity to the plurality of sensors provides greater resolution for determining a concentration of PMPs in the specimen.
A receptacle in accordance with various aspects of the present invention includes an array of wells, each well having an interior surface opposite a surface against which a sensor may be located. By locating a sensor against such a surface, the distance between the sensor and the interior surface is accurately determined, improving assay accuracy results.
In a variation, the receptacle includes an array of wells within a specimen containment wall. Agglomeration of PMPs within a well is avoided. Improved assay accuracy results.